This study is a single arm, open label Phase Ib clinical trial, consisting of two parts: the first part is a safety introduction trial, and the second part is a dose escalation trial. In the first part, the tolerability, safety, PK characteristics, PD characteristics, and preliminary efficacy of VIC-1911 tablets in combination with PTCy and sirolimus will be explored. The first part will conduct safety introduction tests at the same dose as those already tested abroad to determine the dosage required for VIC-1911 tablets to meet safety and effective biological activity. The dose limiting toxicity (DLT) in Phase I study will be evaluated from the first administration of VIC-1911 tablets to 28 days after administration. On this basis, the second part of the experiment will be conducted to further explore the effectiveness and safety of VIC-1911 tablets combined with PTCy and sirolimus under RP2D for preventing GVHD in haplo HSCT patients after myeloablative pretreatment
Children aged 8-18, regardless of gender;
Prior to the start of the study, the subjects and their legal guardians shall sign a written informed consent form;
Patients diagnosed with acute myeloid leukemia or high-risk acute lymphoblastic leukemia who have achieved complete remission (CR) through induction therapy;;
Patients diagnosed with myelodysplastic syndrome (MDS) and with an International Prognostic Scoring System (IPSS, please refer to Appendix 1a) score of medium risk 2 or high risk, or with severe blood cell reduction in the IPSS low-risk group, who have undergone ineffective treatment or have poor prognosis due to genetic abnormalities (such as -7,3q26 rearrangement, TP53 gene mutation, complex karyotype, monomeric karyotype);
Hematopoietic stem cell transplantation comorbidity index (HCT-CI)>4 (Sorror criteria, please refer to Appendix 5);
Plan to start post transplant maintenance treatment within 75 days after transplantation;
Those who are allergic to cyclophosphamide, VIC-1911 tablets, sirolimus, and sirolimus derivatives, or any excipient component of the above drugs;
Those who are unable or unwilling to discontinue other immunosuppressive treatments before the start of the study;
Single group
1mg /kg VIC-1911
DrugVIC-1911 D5-D45 1mg/kg（maximum 75mg）Oral administration on an empty stomach Bid VIC-1911 D5-D45 1.25mg/kg（maximum 75mg）Oral administration on an empty stomach Bid VIC-1911 D5-D45 0.75mg/kg（maximum 75mg）Oral administration on an empty stomach Bid
1.Determine the recommended phase 2 dose (RP2D) of VIC-1911 tablets combined with post transplant cyclophosphamide (PTCy) and sirolimus for the prevention of GVHD in haplo HSCT pediatric patients (Only evaluated in Part 1)
1. The incidence of dose limiting toxicity (DLT) during observation period; 2. When used in combination, the RP2D of VIC-1911 tablets. The dose of RP2D should achieve the minimum expected biological efficacy, and the incidence of DLT in patients at this dose should be less than 30%. The minimum expected biological efficacy is 65% of patients with CD4+pH3ser10+T cells\<54% at baseline by day 21 (-3 to+7), based on the lower confidence interval of pre transplant CD4+pH3ser10+T cell frequency (note: pH3ser10 is the phosphoprotein target of Aurora kinase A)
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Shanghai Jiao Tong University School of Medicine
Lead sponsor
Shanghai Children's Medical Center
Sponsor institution
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